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Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B‐cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.

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Objective:To analyze the factors associated with survival in the largest cohort of individuals with HIV and lymphoma so far described in Brazil.Design:A retrospective, observational, multicenter study involving five institutions in São Paulo, Brazil.Methods:The medical records of consecutive patients with HIV diagnosed with lymphoma between January 2000 and December 2019 were screened. Inclusion criteria consisted of age over 17 years and a biopsy-confirmed diagnosis of lymphoma. The data collected included age, sex, staging (Ann Arbor system), duration of HIV infection, CD4+ lymphocyte count, HIV viral load, lactate dehydrogenase, erythrocyte sedimentation rate and serum beta-2-microglobulin levels, treatment and outcome.Results:Overall, 276 patients were included. Median age was 42 years. Most patients were male (74.3%) and with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (28.6% and 46.4%, respectively). Most had non-Hodgkin lymphomas (89.2%, n = 246), particularly diffuse large B-cell lymphoma (40.9%) and Burkitt lymphoma (26.4%). Hodgkin lymphoma accounted for 9.4%. Advanced stages III/IV were predominant (86.8%). HIV viral load at the moment of lymphoma diagnosis was detectable in 52.9% of patients. A CD4+ cell count of <200 cells/μl was recorded for 53% of the patients. Most patients (62.4%) were on combination antiretroviral therapy. The factors that significantly affected survival were: the ECOG performance status, lymphoma subtype, staging, beta-2-microglobulin level, central nervous system (CNS) infiltration, site of CNS infiltration, relapsed/refractory lymphoma and International Prognostic Index score.Conclusions:HIV status, CD4+-lymphocyte count and relapsed/refractory disease affected survival. Rituximab did not appear to improve outcome in HIV-related lymphomas.

Introduction: Hematopoietic stem cell transplantation (HSCT) is an effective treatment option for patients with hematological and neoplastic diseases. Despite recent improvements, HSCT is still associated with a significant risk of mortality. Determining risk factors for death within the first 100 days after HSCT could help to identify patients who would benefit from interventions in order to decrease that risk. We have previously reported that increased fluid accumulation during conditioning chemotherapy and in the early period after HSCT was associated with decreased survival (Costa EMM et al, ASH 2013Abstract #4512). Herein, we expand that series of patients and we further analyze the impact of weight gain on early (100-days) mortality in patients who underwent HSCT at our institution. Objective: To determine the impact of weight gain during the first 10 days post-HSCT on 100 days mortality. Methods:We retrospectively reviewed the medical charts of 331 patients who underwent HSCT at our institution from January, 2007 until December, 2013. Information on patients' body weight (BW) was measured daily, starting at admission. The highest BW recorded until until the first 10 days post-SCT (D+10) was used to calculate the BW increase in relation to the baseline BW. Based on our previous study, we used a cutoff of 6% gain in BW to identify a group of patients with increased risk of complications. The primary endpoint was mortality within 100 days post HSCT. Overall survival (OS) was estimated from the time of HSCT until death, and surviving patients were censored at last follow-up. A logistic regression model and a Cox model were fit to determine variables that predicted death within 100 days and OS, respectively. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results: Median age was 43 years old (range <1 year-76 years) and 60% were male. HSC sources included autologous (46%), matched related donors (16%), matched unrelated donors (12%), cord blood units (16%) and mismatched related/unrelated donors (10%). Diagnosis included acute leukemia or chronic myeloid disorders (34%), lymphoma/multiple myeloma (42%) and non-malignant hematological disorders (24%). Twenty-one percent of patients had a ≥6% gain in BW until the first 10 days post-HSCT. These patients had developed an increased inflammatory state after the start of the conditioning regimen: there was no difference in baseline levels of C-reactive protein (4.8 mg/L vs. 7.4, p=0.37), but by D+10 patients who gained more BW had higher CRP (116.7 mg/L vs. 178.6 mg/L; p=0.01). Patients with increased gain in BW until D+10 had a decreased OS (HR 2.33, p<0.0001, 95% CI 1.45-3.73). The mortality within 100 days was 47% in the increased BW vs. 17% in the control group (p<0.0001). Among 18 patients who died within 100 days and had a ≥6% BW gain by D+10, causes of death included pneumonia (N=4), septic shock (N=9), fungal endocarditis (N=1), ischemic stroke (N=1) and disease progression (N=3). In a logistic regression analysis, after adjusting for age, sex, diagnosis and type of SCT, a ≥6% BW gain by D10 was associated with an increased risk of being dead within 100 days (coefficient 1.75; p<0.0001; 95% CI 0.90-2.61). Similarly, in a multivariate Cox analysis after adjusting for age, sex, diagnosis and type of SCT, a ≥6% BW gain by D10 was an independent risk factor for survival (HR 2.72, p<0.0001, 95% CI 1.65-4.48). A landmark analysis at D+100 revealed that the negative impact of weight gain by D+10 on survival was restricted to the first 100 days, as after this time point there was no survival difference between the two groups (HR 1.35; p=0.41; 95% CI 0.65-2.83). Conclusion: A ≥6% BW gain by D+10 is a risk factor for early mortality in both autologous and allogeneic HSCT. The most common cause of death in these patients is infectious-related complications. An increase in BW is related to the development of an inflammatory state, probably induced by the conditioning regimen. BW gain is a simple variable that can be easily used to determine prognosis of patients post-allogeneic HSCT, and further studies are needed to determine its etiology. Disclosures No relevant conflicts of interest to declare.

Introduction: The treatment of human hematologic malignancies has rapidly advanced through the application of genomic platforms that have identified drug-able targets and companion diagnostics (e.g. BCR-ABL, IDH-1) and added new classes of targeted agents to the established compendium of cytotoxics. Despite these advances, the complexity, redundancy and promiscuity of cellular transformation remain incompletely understood at the molecular level. This has led to a renewed interest in whole cell experimental models for drug discovery. Laboratory platforms that measure cellular response to cytotoxic insult at the phenotypic level have been shown to correlate significantly with clinical response, and have the capacity to provide insights into chemotherapy selection and drug development. The Ex Vivo Analysis of Programmed Cell Death (EVA/PCD) uses metabolic and morphologic features of drug induced cell death to measure both cytotoxic and targeted drug effects in human primary cultures. We applied EVA/PCD in 20 heavily pre-treated, drug refractory patients from the Hospital Israelita Albert Einstein (HIAE) in Sao Paulo - Brazil. Methods: Peripheral blood, node biopsy or bone marrow aspirates were submitted by overnight courier. Cells isolated by density centrifugation were evaluated by dose response curves that were interpolated to provide LC50 values for comparison with our databases by Z-score. Patients with Acute Lymphoblastic Leukemia (ALL, N=5) , Acute Myeloid Leukemia (AML, N=6), Non-Hodgkin Lymphoma (NHL, N=4) or Multiple Myeloma (MM, N=4) had received a mean of 5, median of 4 (range 1-8) prior therapies, 7 with prior bone marrow transplantation (BMT). Results: of 20 specimens, 16 (80%) provided viable tumor for EVA/PCD. A mean of 8, median of 7(range 3-22) cytotoxics and a mean 7, median of 5(range 1-20) targeted agents were evaluated. Findings were reported by day 7. Nine of 16 patients were treatment candidates, with 5 lost to follow up, 3 dying of sepsis before evaluation and 1 achieving complete remission (CR) with radiation plus Rituximab. Of 7 patients who received assay directed therapy there were 3 CR (43%), 2 partial responses (PR: 28%) and 2 progressive disease (PD: 29%) for an overall response rate of 71%. Conclusion: These results establish the feasibility of laboratory directed therapy in heavily pre-treated patients, with 80% of submitted samples providing actionable results. Although the extremely advanced state of these patients limited the capacity to undergo treatment in some cases, the achievement of CR's and PR's in this drug refractory cohort is of interest. Clinical responses by disease, treatment history and drugs received will be reported. Studies correlating molecular profiles with phenotypic analyses are currently under development. Disclosures Evans: Rational Therapeutics: Employment. Nagourney:Rational Therapeutics: Employment.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) corresponds to a wide array of potentially fatal hyper-inflammatory diseases involving pathologic immune activation and engulfment of hematopoietic cells by activated macrophages. These disorders have common clinical and laboratorial features, such as severe cytopenias, fever, hepatosplenomegaly and hyperferritinemia, leading to a dismal prognosis when treatment is delayed. Secondary hemophagocytic syndromes may develop as a result of strong immunological activation of the mononuclear phagocyte system by underlying conditions, such as infection, autoimmune diseases, malignancies and metabolic disorders. Mortality rates are high, even with proper treatments, and can reach up to 50%, usually within the first two months of the diagnosis. Diagnosis of this condition is difficult and requires a high degree of suspicion, since the diagnostic criteria are non-specific. Up to 30% of patients with confirmed hemophagocytic syndrome do not show this morphologic aspect in bone marrow examination. We report the data of our institution, regarding the clinical aspects, treatment and outcome of patients with confirmed hemophagocytosis in bone marrow aspiration analysis. Objective: To determine clinical aspects underlying the development of secondary hemophagocytosis and the outcome of patients with this condition. Methods: We retrospectively reviewed all bone marrow aspirations conducted from January, 2012 until December, 2013, regardless of diagnosis. A total of 1682 examinations were performed during this period and reevaluated by three specialists. We found 45 patients with cytological evidence of hemophagocytosis. The medical charts of these patients were reviewed and the following data was retrieved: age, gender, presence of fever and hepatosplenomegaly, underlying disease, past medical history, known underlying immunosuppression, treatment and outcome. Laboratory data was evaluated in the day of the bone marrow aspiration or in the two preceding or following days and included: hemoglobin, leucocytes and platelets counts; ferritin; triglycerides; fibrinogen, lactate dehydrogenase. Diagnosis criteria were defined accordingly to the guidelines of the Hemophagocytic Lymphohistiocytosis Study Group, published in 2004, excluding the soluble CD25 and NK cell activity assays that were unavailable. Results: Median age was 52 years old (range <1 year-72 years) and 58% were male. Twenty-six (57%) had a diagnosis of neoplasia (21 hematological and 5 solid organ malignancies), and 3 patients had recently underwent bone marrow transplantation. Eighteen patients (40%) were receiving immunosuppressive therapy. Evidence of ongoing infection was identified in 34 cases (75.5%), and in 61.8% the agent was identified. Viral infections were commonly associated (26%), and in our case series, cytomegalovirus was the most implicated agent (5 cases). Other virus found were Parvovirus B19, H1N1, Parainfluenza, Herpes-Virus 6 and Epstein-Barr Virus. Bacterial and fungal infections were each responsible for 28,8% of the cases, and in 13 cases (38,2%) the agent was not identified. Among the patients who had complete laboratory evaluation (27 patients), we found that only 37% presented with all diagnostic criteria. Mortality rate was 35.5%, and median survival was 23 months (95% CI 22-60), with most deaths taking place in the first two months. None of the patients received specific treatment, being treated exclusively for the underlying conditions. Conclusion: Secondary hemophagocytic syndrome is a rare yet severe condition, usually associated with a high mortality rate. In most cases, the diagnosis is not suspected and proper treatment not applied. Diagnosis criteria lack specificity and are more useful to the diagnosis of familial forms of HLH. The most common underlying conditions appear to be malignancies, infections and transplant-related immunosuppression. Treatment of the underlying conditions alone still retains large failure rates, and efforts must be made to achieve early diagnosis and employment of therapy. Disclosures No relevant conflicts of interest to declare.